There is a well-established association between postmenopausal estrogen replacement and decreased rates of coronary heart disease among women. Estimates of reduction range from about 50% to as much as 70%. Poor compliance with estrogen replacement therapy by postmenopausal women has prevented a major impact on the public health since only about 8% of women continue the treatment over the years in which prevention of coronary heart disease and osteoporosis are important. We have sought to identify an alternative regimen that would be more acceptable to women and still provide protection against coronary heart disease and osteoporosis. Specifically, we propose to compare the therapeutic/prophylactic benefits of conjugated equine estrogens and soybean estrogens in the prevention of postmenopausal coronary artery atherosclerosis/dysfunction, osteoporosis, and mammary gland and endometrial hyperplasia/dysplasia (monkey studies) and compare their effects on progression of carotid artery atherosclerosis, changes in bone density, and quality of life/compliance issues (human studies). The rationale is based upon the putative protective effect of these compounds against the development of breast cancer and osteoporosis, the likely lack of a harmful effect on the uterus, and an experimental basis for assuming probable favorable effects on coronary artery atherosclerosis. The Program Project takes advantage of the capabilities of our institution in conducting randomized trials in both human and nonhuman primates and the capabilities for exploring mechanisms of mammalian and plant estrogen effects on atherogenesis and vascular function.